MOZART1 and gamma-tubulin complex receptors are both required to turn gamma-TuSC into an active microtubule nucleation template

作者：Lin Tien Chen; Neuner Annett; Flemming Dirk; Liu Peng; Chinen Takumi; Jaekle Ursula; Arkowitz Robert; Schiebel Elmar^*

来源：The Journal of Cell Biology, 2016, 215(6): 823-840.

DOI：10.1083/jcb.201606092

MOZART1/Mzt1 is required for the localization of gamma-tubulin complexes to microtubule (MT)-organizing centers from yeast to human cells. Nevertheless, the molecular function of MOZART1/Mzt1 is largely unknown. Taking advantage of the minimal MT nucleation system of Candida albicans, we reconstituted the interactions of Mzt1,gamma-tubulin small complex (gamma-TuSC), and gamma-tubulin complex receptors (gamma-TuCRs) Spc72 and Spc110 in vitro. With affinity measurements, domain deletion, and swapping, we show that Spc110 and Mzt1 bind to distinct regions of the gamma-TuSC. In contrast, both Mzt1 and gamma-TuSC interact with the conserved CM1 motif of Spc110/Spc72. Spc110/Spc72 and Mzt1 constitute "oligomerization chaperones," cooperatively promoting and directing gamma-TuSC oligomerization into MT nucleation-competent rings. Consistent with the functions of Mzt1, human MOZ ART1 directly interacts with the CM1-containing region of the gamma-TuCR CEP215. MOZ ART1 depletion in human cells destabilizes the large gamma-tubulin ring complex and abolishes CEP215(CM1)-induced ectopic MT nucleation. Together, we reveal conserved functions of MOZ ART1/Mzt1 through interactions with gamma-ubulin complex subunits and gamma-TuCRs.

• 出版日期2016-12-19